Transcriptome and Secretome Profiling of Sensory Neurons Reveals Sex Differences in Pathways Relevant to Insulin Sensing and Insulin Secretion

Authors

Sohyun Moon, Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, USA.
Lamyaa Alsarkhi, Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USA.
Tai-Tu Lin, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Ryota Inoue, Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, Japan.
Azeddine Tahiri, Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USA.
Cecilia Colson, The Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.
Weikang Cai, Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, USA.
Jun Shirakawa, Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, Japan.
Wei-Jun Qian, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Jerry Yingtao Zhao, Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, USA.
Abdelfattah El Ouaamari, Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USA.

Author Type(s)

Faculty

DOI

10.1096/fj.202300941R

Journal Title

FASEB Journal

First Page

e23185

Document Type

Article

Publication Date

10-1-2023

Department

Cell Biology and Anatomy

Abstract

Sensory neurons in the dorsal root ganglia (DRG) convey somatosensory and metabolic cues to the central nervous system and release substances from stimulated terminal endings in peripheral organs. Sex-biased variations driven by the sex chromosome complement (XX and XY) have been implicated in the sensory-islet crosstalk. However, the molecular underpinnings of these male-female differences are not known. Here, we aim to characterize the molecular repertoire and the secretome profile of the lower thoracic spinal sensory neurons and to identify molecules with sex-biased insulin sensing- and/or insulin secretion-modulating activity that are encoded independently of circulating gonadal sex hormones. We used transcriptomics and proteomics to uncover differentially expressed genes and secreted molecules in lower thoracic T5-12 DRG sensory neurons derived from sexually immature 3-week-old male and female C57BL/6J mice. Comparative transcriptome and proteome analyses revealed differential gene expression and protein secretion in DRG neurons in males and females. The transcriptome analysis identified, among others, higher insulin signaling/sensing capabilities in female DRG neurons; secretome screening uncovered several sex-specific candidate molecules with potential regulatory functions in pancreatic β cells. Together, these data suggest a putative role of sensory interoception of insulin in the DRG-islet crosstalk with implications in sensory feedback loops in the regulation of β-cell activity in a sex-biased manner. Finally, we provide a valuable resource of molecular and secretory targets that can be leveraged for understanding insulin interoception and insulin secretion and inform the development of novel studies/approaches to fathom the role of the sensory-islet axis in the regulation of energy balance in males and females.

Recommended Citation

Moon, S., Alsarkhi, L., Lin, T., Inoue, R., Tahiri, A., Colson, C., Cai, W., Shirakawa, J., Qian, W., Zhao, J. Y., & El Ouaamari, A. (2023). Transcriptome and Secretome Profiling of Sensory Neurons Reveals Sex Differences in Pathways Relevant to Insulin Sensing and Insulin Secretion. FASEB Journal, 37 (10), e23185. https://doi.org/10.1096/fj.202300941R